Known in the art is a complex platinum compound, viz. cis-dichlorodiamine platinum(II) (DDP) (Nature; vol. 222, 1969 (Macmillan (Journals) LTD, London) B. Rosenberg, L. Van Camp, J. E. Trosko, V. H. Mansour: "Platinum Compounds; A New Class of Antitumor Agents", p. 385).
This platinum compound has the formula: ##STR2## and reveals a high antitumor activity.
It possesses a remarkably wide spectrum of action on diverse tumors, activity in respect of rapidly growing and slowly developing neoplasms, as well as activity in respect of not only early-formed (small-size) neoplasms but also in respect of well-formed and even far-gone and disseminated neoplasms; it is also characterized by the absence of typical specificity.
Nevertheless, likewise all antitumor compounds, in addition to the effect on neoplasms, DDP exhibits a toxic effect the organism, thus limiting dosage of this compound and frequently forcing discontinuation of the treatment due to a toxic effect of the compound on kidney. The LD.sub.50 of this platinum complex (the dose at which 50% of the test animals are dead) is the same for mice and rats--about 13 mg/kg (Vestnik AMN SSSR, No. 2, 1979 (Medicina, Moscow); M. A. Presnov, A. L. Konovalova, V. P. Koral'chuk "Complex Compounds of Platinum in Chemotherapy of Malignant Tumors", p. 72).
Furthermore, an insufficient solubility of DDP in water (0.25 mass % at 25.degree. C.) complicates the use of this preparation in clinics and makes it impossible to carry out a local treatment of the tumor with a solution containing a high concentration of the preparation.
Also known in the art are platinum(II) dichlorocomplexes with two molecules of primary alicyclic amines, beginning with cyclopropylamine and ending with cyclooctylamine also revealing antitumor properties and corresponding to the formula: ##STR3## wherein n is 1 to 6 (Chem.-Biol. Interaction, vol. 5, 1972, Elsevier, Netherlands): T. A. Connors, M. Jones, W. C. J. Ross, P. D. Braddock, A. R. Khokhar, M. L. Tobe "New platinum complexes with antitumor activity", see p. 421-422). Chem.-Biol. Interaction, vol. 11, 1975 (Elsevier, Netherlands): P. D. Braddock, T. A. Connors, M. Jones, A. R. Khokhar, D. H. Melzack, M. L. Tobe "Structure and activity relationships of platinum complexes with antitumor activity", p. 153).
On regrafted plasmacytoma of mice ADJ/PC6A these complexes show a high antitumor activity, the highest selectivity of their action is observed for complexes with cyclopentyl- and cyclohexylamine (therapeutical indexes (TI/equal to the ratio of the LD.sub.50 to the inhibiting dose (ID) suppressing growth of the tumor by 90%, TI=LD.sub.50 /ID.sub.90 are equal to 200 and above 267 respectively). These very high therapeutical index values have caused clinical tests of cis-[PtCl.sub.2 (cyclo-C.sub.5 H.sub.9 NH.sub.2).sub.2 ] (cf. Cancer Treatment Reports, vol. 63, No. 9-10, September-October 1979 (national Cancer Institute, Bethesda); J. M. Hill, E. Loeb, A. Pardue, A. Khan, J. J. King, C. Aleman, N. O. Hill "Platinum Analogs of Clinical Interest", see p. 1510, 1512).
This compound, however, is substantially insoluble in water, wherefore it should be administered in the form of fine suspensions in sesame oil or in the form of aqueous solloids stabilized by polyvinylpyrrolidone. The administration of the compound in these forms has shown that it substantially remains at the spot of the injection and no therapeutic response or a side effect, apart from a local irritation upon administration of an oily suspension, is observed, wherefore further tests were stopped.
Known in the art is also a mixed chloride platinum(II) complex containing ammonia and cyclopentylamine having formula: cis-[PtCl.sub.2 NH.sub.3 (cyclo-C.sub.5 H.sub.9 NH.sub.2)] (cf. British Pat. No. 2,060,615A Cl. C 07 F 15/00, A 61 K 31/555 published in 1981).
Tests of the compound on a regrafted plasmacytoma of mice ADJ/PC6A have shown that the compound is slightly more toxic than DDP (LD.sub.50 are 11.0 and 13.0 mg/kg respectively), but it inhibits growth of tumors by 90% in a dose which is by 3 times as less as that of DDP and nearly 5 times as less as that of cis-[PtCl.sub.2 (cyclo-C.sub.5 H.sub.9 NH.sub.2).sub.2 ]/ID.sub.90 is equal to 0.5, 1.6 and 2.4 mg/kg respectively).
However, in the paper (Cancer Treatment Reports, vol. 63, No. 9-10, September-October, 1979 (National Cancer Institute, Bethesda): T. A. Connors, M. J. Cleare, K. R. Harrap "Structure-Activity Relationships of the Antitumor Platinum Coordination Complexes", see p. 1501) a conclusion is made to the effect of absence of advantages of this mixed complex as compared to the parent compounds with identical ligands.
As regards solubility in a 0.9% NaCl (about 1 mg/ml), the mixed platinum complex does not differ from DDP (see J. E. Schurig, W. T. Bradner, J. B. Huftalen, G. J. Doyle, J. A. Gylys "Toxic side effects of platinum analogs" in: A. W. Prestyako, S. T. Crooke (Eds.) Cisplatin Current Status and New Developments", 1980, Academic Press (New York), see p. 228, 230).
For the synthesis of this mixed complex of platinum a known method of synthesis of such compounds has been used which is based on interaction of the complex K [PtCl.sub.3 (NH.sub.3)] with cyclopentylamine. The yield of the purified product is 4.8% (see the British Patent referred to hereinabove).